Semisynthetic, site-specific ubiquitin modification of α-synuclein reveals differential effects on aggregation

J Am Chem Soc. 2012 Mar 28;134(12):5468-71. doi: 10.1021/ja300094r. Epub 2012 Mar 14.


The process of neurodegeneration in Parkinson's Disease is intimately associated with the aggregation of the protein α-synuclein into toxic oligomers and fibrils. Interestingly, many of these protein aggregates are found to be post-translationally modified by ubiquitin at several different lysine residues. However, the inability to generate homogeneously ubiquitin modified α-synuclein at each site has prevented the understanding of the specific biochemical consequences. We have used protein semisynthesis to generate nine site-specifically ubiquitin modified α-synuclein derivatives and have demonstrated that different ubiquitination sites have differential effects on α-synuclein aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Disulfides / chemistry
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Parkinson Disease / metabolism
  • Protein Conformation
  • Ubiquitin / chemistry*
  • Ubiquitin / metabolism
  • Ubiquitination
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / metabolism


  • Disulfides
  • Ubiquitin
  • alpha-Synuclein